Plasma concentrations of tricyclic antidepressants were monitored during treatment of 126 patients. Noncompliance in taking medication was suspected in 19 patients because of unusually low plasma concentrations in relation to the presumed dose. Determinations of plasma concentrations may also be useful for detecting inadequate treatment as judged by levels below the presumed therapeutic range. Attempts to correlate plasma concentrations with clinical response to amitriptyline hydrochloride and nortriptyline hydrochloride failed, probably because of the heterogeneity of depressive syndromes being treated. Plasma concentrations were correlated highly with dose in the case of amitriptyline, less so in the case of other drugs. Amitriptyline and imipramine hydrochloride generally produced plasma concentrations of the parent drug and metabolite higher in nanograms per milliliter than was the daily dose in milligrams; nortriptyline and desipramine hydrochloride did the opposite.